Opening up the Long-Awaited EU Pharmaceutical Package

On April 26, 2023, the European Commission finally published its long-awaited EU Pharmaceutical Package. This Package introduces new draft legislation that would revise and replace existing EU pharmaceutical legislation in line with the Pharmaceutical Strategy for Europe, which was adopted by the EU on November 25, 2020.

The Pharmaceutical Strategy, which is clearly reflected in the Commission’s new proposals, is based on the following four pillars:

• Ensuring access to affordable medicines for patients, and addressing unmet medical needs;
• Supporting competitiveness, innovation and sustainability of the EU’s pharmaceutical industry and the development of high-quality, safe, effective and greener medicines;
• Enhancing crisis preparedness and response mechanisms, diversified and secure supply chains, addressing medicines shortages; and
• Ensuring a strong EU voice in the world, by promoting a high level of quality, efficacy and safety standards.

To achieve these goals, the Commission has proposed two new measures that would revise and replace the existing EU general pharmaceutical legislation:

• A proposed Directive on the Union code relating to medicinal products for human use (repealing Directives 2001/83/EC and 2009/35/EC); and
• A proposed Regulation laying down Union procedures for the authorization and supervision of medicinal products for human use and establishing rules governing the European Medicines Agency (amending Regulations (EC) No 1394/2007 and (EU) No 536/2014, and repealing Regulations (EC) No 726/2004, (EC) No 141/2000 and (EC) No 1901/2006).

In addition to these two proposals, the European Commission has also proposed a Council Recommendation to step up the fight against antimicrobial resistance.

The most significant proposed changes for the pharmaceuticals industry are:

1. A reduction in the regulatory data protection period (Articles 80 – 84 of the proposed Directive)

The proposed Directive would reduce the regulatory data protection period to six years (instead of the current eight years). However, subject to stringent conditions, it would be possible to prolong this period, by:

• two years (or even three years for, e.g., small and medium-sized enterprises) if the market authorization (MA) holder can demonstrate that within two years from the date of the MA, the medicinal product has been released and continuously supplied in a sufficient quantity and in the presentations necessary to cover the needs of patients in all Member States in which the MA is valid;
• six months on condition that the MA holder demonstrates that the medicinal product addresses an unmet medical need;
• six months on condition that the clinical trials supporting the initial MA application use a relevant and evidence-based comparator following the scientific advice of the European Medicines Agency (EMA); or
• one year on condition that the MA holder obtains authorization for a new therapeutic indication which demonstrates a significant clinical benefit in comparison with existing therapies during the initial regulatory data protection period.

The proposed Directive also allows for repurposed medicinal products to be granted a regulatory data protection period of four years with respect to a new therapeutic indication, provided that it has been demonstrated that this therapeutic indication is of significant clinical benefit and that the medicinal product has not previously benefited from data protection, or twenty-five years have passed since the granting of the initial MA.

If a compulsory license has been granted to a party to address a public health emergency, both the data and market protection period can be suspended with regard to that party insofar as the compulsory license requires.

2. Data exclusivity voucher for priority antimicrobials (Articles 40 – 43 of the proposed Regulation)

According to the proposed Regulation, an applicant for an MA may be granted a transferable data exclusivity voucher to a “priority antimicrobial.” An antimicrobial is considered a “priority antimicrobial” if preclinical and clinical data underpin a significant clinical benefit with respect to antimicrobial resistance and it has at least one of the following characteristics: i) it represents a new class of antimicrobials, ii) its mechanism of action is distinctly different from that of any authorized antimicrobials, or iii) it contains an active substance not previously authorized in a medicinal product that addresses a multi drug resistant organism or a serious or life threatening infection.

If granted, the voucher would allow the applicant the right to one additional year of data protection for any authorized medicinal product, which can be the priority antimicrobial or any other medicinal product. The voucher can only be used once and in relation to a single centrally authorized medicinal product, and only if that product is within its first four years of regulatory data protection.

3. Bolar exemption (Article 85 of the proposed Directive)

The proposed Directive would significantly extend the scope of the Bolar exemption. In addition to the established exemption in the context of activities to obtain a generic or biosimilar MA, the newly proposed exemption also allows conducting studies, trials and other activities to generate data for hybrid or biohybrid medicinal products and subsequent variations. Furthermore, activities for health technology assessments and pricing and reimbursement procedures are expressly included in the exemption.

Under the existing EU general pharmaceutical legislation, there has been some doubt as to whether the Bolar exemption also applies to commercial suppliers of active ingredients if they supply patented products to generic manufacturers for conducting trials to obtain an MA (see Astellas v Polpharma (C-661/13)). The proposed Bolar exemption puts an end to this discussion by making it explicitly applicable to third-party suppliers and service providers.

4. Orphan medicinal products (Articles 63 – 73 of the proposed Regulation)

In order to facilitate and expedite the designation procedure, the competence to designate a medicinal product as an orphan medicinal product is accorded to the EMA.

The duration of market exclusivity is set at nine years (instead of the current ten-year period), except for (i) orphan medicinal products that address a high unmet medical need, which will benefit from ten years, and (ii) well-established use orphan medicinal products, which will be granted only five years of market exclusivity. Except for well-established use orphan medicinal products, the market exclusivity can be prolonged by a maximum of three years:

• • • an additional year of market exclusivity if at least two years before the end of the exclusivity period, the orphan MA holder obtains a new MA for one or more new therapeutic indications for a different orphan condition. Such a prolongation may be granted twice, if the new therapeutic indications are each time different orphan conditions.
    • in addition, orphan medicinal products can benefit from a “bonus” market exclusivity extension of one year, based on patient access in all relevant Member States.

5. Pediatric medicinal products (Article 60 and 86 of the proposed Directive and Articles 74 – 98 of the proposed Regulation)

The proposed legislation would mean that when a pediatric use MA is granted and includes the results of all studies conducted in compliance with an agreed pediatric investigation plan, the product would benefit from independent data and marketing protection periods and the holder of the patent or the supplementary protection certificate (SPC) would be granted a six-month extension of the SPC.

The new EU Pharmaceutical Package foresees that if such an MA holder has benefited from rewards (e.g., the extension of the SPC) and these periods have expired, and the MA holder intends to discontinue placing the medicinal product on the market, the MA holder must transfer the MA to a third party or allow a third party to use the pharmaceutical, non-clinical and clinical documentation.

6. Environmental risk assessment (Article 47 of the proposed Directive and Articles 7 – 12 of the proposed Regulation)

The conditions relating to environmental risk assessment (ERA) are strengthened in the proposed legislation. MA applications must include an ERA and risk mitigation measures. If the applicant fails to submit a complete or sufficiently substantiated ERA, or if the applicant does not propose risk mitigation measures sufficiently addressing the risk identified in the ERA, the MA will be refused. The ERA must be updated when new data or knowledge about relevant risks becomes available.

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Substantial amendments to this proposed legislation can be expected. Nonetheless, it is already clear that the EU Pharmaceutical Package will, when adopted, have significant consequences for both the pharmaceuticals industry and for patients. We will continue to follow up these developments, and our Crowell & Moring Life Sciences team is here to answer any questions you may have and to provide you with ongoing updates.